Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-01-14 to 1999-06-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a draft OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guideline for Testing of Chemicals, Draft OECD Guideline, Dermal Delivery and Percutaneous Absorption: In Vitro Method, June 1996
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethylbis(octadecyloxy)silane
EC Number:
249-385-9
EC Name:
Dimethylbis(octadecyloxy)silane
Cas Number:
29043-70-7
Molecular formula:
C38H80O2Si
IUPAC Name:
dimethylbis(octadecyloxy)silane
Test material form:
other: solid

Test animals

Species:
pig
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
n/a

Administration / exposure

Vehicle:
ethanol
Duration of exposure:
24 hours
Doses:
- Actual doses: 3 mg/mL in 40 % ethanol
- Dose volume: 1 mL of test item in ethanol
No. of animals per group:
n/a
Control animals:
yes
Remarks:
negative control: ethanol; positive control: caffeine
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: test material was suspended in 40 % ethanol
- Method of storage: no data

APPLICATION OF DOSE: 3 mg/ml

VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol was chosen because of its solubility properties and non-toxicity to the skin

TEST SITE
- Preparation of test site: the skin was washed, cleaned and shaved from hair, then the skin was removed by dissection
- Area of exposure: eat skin

REMOVAL OF TEST SUBSTANCE
The test substance was applied to the skin throughout the skin penetration test

ANALYSIS
- Method: atom absorption spectroscopy (AAS)

SAMPLE PREPARATION
- Storage procedure: stored at -20 °C after collection, shipped at room temperature and stored at room temperature before analysis
- Preparation details:

SKIN INTEGRITY
- Conductivity across the skin was measured at each sampling time
- Skin damages are indicated by sudden increase in conductivity
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Rambaud slaughter house
- Ethical approval if human skin: not applicable
- Type of skin: porcine ear skin
- Preparative technique: the outer region of the ear was washed and cleaned, the hair was shaved and the skin was removed by dissection
- Thickness of skin (in mm): 0.5 mm
- Membrane integrity check: Integrity was monitored over the entire duration of the study by measuring conductivity across the skin at each sampling time. Skin damage is indicated by a sudden increase in conductivity or unsteady slopes of the measured values over time.
- Storage conditions: no data
- Justification of species, anatomical site and preparative technique: porcine skin has shown to give comparable results to those obtained from human skin.

PRINCIPLES OF ASSAY
The skin was mounted in a glass flow through diffusion chamber with a diameter of 1.135 cm and volume of 1 ml (donor chamber). The upper part was the donor chamber and the lower part-acceptor chamber. The acceptor chamber was filled with 40 % ethanol at the beginning of the experiment. Ethanol was pumped through the chambers using a 6-channel peristaltic pump with a flow rate of 1-2 ml/hour/chamber. The eluent of the acceptor chamber was collected in plastic vials, which were stored at -20°C until analysis. The donor chamber was filled with 3 mg/ml test material in 40 % ethanol and covered with paraffin. The whole system was set up in an incubator at 32°C. The collecting vials were changed at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours. The rate of absorption was calculated by determination of the test substance concentration in the collecting vials.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): no relevant skin absorption was observed at any time point within the time frame of the experiments.

Percutaneous absorption
Dose:
3 mg/ml
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: 0, 0.5, 1, 2, 4, 6, 8 and 24 hours
Remarks:
No measurable penetration of the skin occurred at any time point within the time frame of the test.

Any other information on results incl. tables

Air bubbles were observed in all of the receptor chambers after 24 hours possibly blocking some of the skin area. However, since the conductivity across the skin was hardly affected, even after 24 hours, it was judged that the air bubbles did not have any relevant effect on the skin penetration.

Applicant's summary and conclusion

Conclusions:
In the skin permeability study for dimethylbis(octadecyloxy)silane, conducted according to a draft OECD Test Guideline, and in compliance with GLP, no skin penetration of the test substance was observed.